Impact and Cost-effectiveness of Safer Conception Strategies for HIV prevention This mentored research project will investigate an urgent public health problem that has been neglected in HIV prevention research: the reproductive needs of HIV-discordant couples who desire pregnancy. Across sub-Saharan Africa, the vast majority of HIV-infected individuals are adults of reproductive age. The HIV prevention literature has almost exclusively focused on strategies to prevent sexual HIV transmission in the context of promoting 100% condom use, which is not compatible with conception, and strategies to prevent HIV after conception has occurred, e.g., prevention of transmission from mother to child during pregnancy, labor and delivery, or breastfeeding. While several reviews on safer conception and HIV prevention have been published and clinical guidelines have recently been developed, there has been no systematic research to examine the costs, potential impact and cost-effectiveness, or actual preferences for different strategies of safer conception. My proposed mentored research plan will address this critical gap in HIV prevention research. It is comprised of two phases: the first phase a small mixed methods demonstration project to pilot test the safer conception guidelines in Kenya; and the second, a study to estimate costs and model the potential impact and cost- effectiveness of the guidelines.These phases will address the following aims: (1) Conduct a mixed-methods demonstration project to (i) characterize adherence to and preferences for different safer conception strategies, and (ii) estimate parameters necessary to model the impact of and design a large-scale evaluation of a combination safer conception program in this setting. I will, with a Kenyan research team, use quantitative and qualitative methodologies to characterize uptake, adherence to, and patient and provider preferences for different safer conception strategies, and generate critical preliminary estimates of process and impact outcomes, and inter-clinic variability in outcomes. The findings from this work will lay the groundwork for Aims 2 and 3; (2) Estimate the cost, and model the impact and cost-effectiveness of different strategies for safer conception for HIV-discordant couples in Nyanza Province, Kenya. I will carry out micro- costing and time and motion studies during the implementation of the demonstration project (above) to gather estimates on resources required for providing safer conception options. I will use data from the demonstration project and appropriate historical cohorts to model the potential impact and cost-effectiveness of different strategies of safer conception interventions for HIV prevention among discordant couples in this setting; (3) Develop a preliminary plan for a combination safer conception intervention to prevent HIV transmission among HIV discordant couples in Nyanza. In participatory workshops with local stakeholders, we will critically evaluate the research findings, identify potential challenges, define the safer conception intervention package, and develop an intervention plan. In year 4, I will submit an R-series application to the NIH for a large-scale study to determine the impact and estimate the cost-effectiveness of the intervention.